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G H Heppner

Publications and source records attributed to G H Heppner.

At least 91 records · Page 5Linked to original sources
PubMed1979

Immunologic heterogeneity of tumor cell subpopulations from a single mouse mammary tumor.

Five subpopulations (66, 67, 68H, 168, and 4.10LM) obtained from a single BALB/cfC3H mammary adenocarcinoma were used to assess intratumor immunologic heterogeneity. BALB/c and BALB/cfC3H mice were immunized with each of the subpopulations, and lymph node cells (LNC) from immunized animals were tested for cell-mediated immunity (CMI) to each subpopulation in vitro by chromium release and microcytotoxicity tests and in vivo by Winn assays. The immunogenic character of the subpopulations differed markedly. The pattern of cross-reactivity indicated that at least two determinants were involved, one of which was probably a viral antigen. The viral antigen was expressed on 4 subpopulations (66, 68H, 168, and 4.10LM). The other determinant was immunogenic in both BALB/c and BALB/cfC3H mice and was expressed on 4 subpopulations (66, 67, 168, and 4.10lm). Thus 1 subpopulation (68H) expressed only the viral antigen, 1 (67) expressed only the other antigen, and 3 (66, 168, and 4.10LM) expressed both. Expression of the determinants showed qualitative and quantitative variations. Quantitative differences were noted by the relative effectiveness of the subpopulations to induce CMI and by the relative sensitivities to LNC-mediated killing. Qualitative differences were indicated by the occurrence of unidirectional cross-reactivities between some pairs of subpopulations; a determinant could be expressed so that the subpopulation could induce cytotoxic cells but not be sensitive to them or vice versa.

Adenocarcinoma↗
PubMed1978

Effect of chemical carcinogen treatment on the immunogenicity of mouse mammary tumors arising from hyperplastic alveolar nodule outgrowth lines.

The experiments reported herein examined the effects of chemical carcinogen treatment of precursor hyperplastic alveolar nodules on the immunogenicity of subsequent mammary tumors in mice. The results of in vitro immunogenicity assays were compared with those of in vivo transplantation resistance tests. This comparison demonstrated that the in vitro assays predicted qualitatively and quantitatively the results from the in vivo test. In addition, the data suggested that the immunogenicity of a tumor depends on events occurring during the development of precursor hyperplastic alveolar nodules rather than during the development of subsequent mammary tumors.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1978

Heterogeneity of tumor cells from a single mouse mammary tumor.

By the use of a variety of cell culture and separation methods, four cell lines were isolated from a single autochthonous BALB/cfC3H mammary tumor. These lines differ markedly from each other in culture morphology, various in vitro growth properties, expression of murine mammary tumor virus antigen, and karyotype, yet all four lines are tumorigenic in normal, syngeneic hosts, yielding tumors of generally similar histology, although distinct from the original neoplasm. Three of the four lines have been cloned from soft agar. The clones exhibit the same growth properties as the lines from which they were derived. Karyotypic analysis of the parent tumor revealed the presence of cells with heterogeneous numbers of chromosomes similar to those seen in the isolated lines, suggesting both the presence of these distinct cell types in the original neoplasm and a genetic origin of the diversity.

Adenocarcinoma↗
PubMed1978

In situ lymphoid cells of mouse mammary tumors. I. Development and evaluation of a method for the separation of lymphoid cells from mouse mammary tumors.

A method of separating lymphoid cells from solid mouse mammary tumors was developed and evaluated. In this method the tumors are digested with 0.01% collagenase, 0.01% DNAase, and 0.025% trypsin in Dulbecco's PBS into suspensions of cells with a viability of 90%. The suspensions are fractionated on a continuous gradient of Ficoll in tissue culture medium. In model experiments this gradient was found to separate, cleanly, admixed cells of an established mammary tumor cell line and dissociated thymus glands. Recovery rates were 50% for the tumor cells and 80% for the thymocytes. The preparation of the cell suspensions and the gradient separation procedure are not harmful to the cells as indicated by trypan blue exclusion and the ability to grow in cell culture.

Animals↗
PubMed1978

In situ lymphoid cells of mouse mammary tumors. II. The characterization of lymphoid cells separated from mouse mammary tumors.

Lymphoid cells were isolated from mouse mammary tumors by isokinetic gradient centrifugation. theta-bearing and ALS-sensitive cells were always the largest subpopulations found in these tumors. In fractions 4 to 6 from the isokinetic gradient, theta-positive cells ranged from 8 to 46% in autochthonous tumors and 14 to 47% in passaged tumors, and ALS-positive cells ranged from 34 to 46% in autochthonous tumors and 14 to 100% in passaged tumors. SIg-positive cells were only found in occasional tumors and, where present, averaged 2% of the separated population. Fc receptor-bearing cells averaged 15% and phagocytic cells averaged 8% of the cells found in fractions 4 to 6 of the gradient. Occasional ALS-positive and one-third of the Fc receptor-bearing and phagocytic cells also separated in fractions 7 to 10 of the isokinetic gradient. Although the individual tumors were very variable in the proportions of the various lymphoid subpopulations that they contained, this variability was a stable characteristic for at least one passage generation.

Animals↗
PubMed1978

In situ lymphoid cells of mouse mammary tumors. III. In vitro stimulation of tumor cell survival by lymphoid cells separated from mammary tumors.

Lymphoid cells were isolated by isokinetic gradient centrifugation from mouse mammary tumors and evaluated for their ability to affect tumor cell survival with the microcytotoxicity assay. In all experiments stimulation of the growth or survival of tumor cells was seen. This stimulation was not seen with separated lymphoid cells treated with anti-lymphocyte serum and complement. The lymphoid cells separated from tumors were more stimulatory than were lymph node cells; even toxic to the tumor cells, the separated tumor-associated lymphoid cells were markedly stimulatory. The gradient procedure had no effect on the activity of sensitized lymph node cells, but it did separate cytotoxicity and stimulation into different fractions.

Animals↗
PubMed1978

Heterogeneity in drug sensitivity among tumor cell subpopulations of a single mammary tumor.

Three distinct subpopulations of tumor cells derived from a single parent strain BALB/cfC3H mammary adenocarcinoma were tested in vivo for sensitivity to cyclophosphamide, methotrexate, and 5-fluorouracil. Treatment was begun either 2 days after s.c. tumor cell injection or at the time when the tumors became palpable. It was given on a weekly basis for 4 weeks. The mice were observed for growth of the primary implant and for development of spontaneous metastases. The three subpopulations differed markedly in their sensitivity to the drugs. The effects of the drugs ranged from induction of regression of the "primary" to enhancement of metastases. The effect on primary growth was independent of that on metastasis. The effect of the time of administration of the drugs also varied among the subpopulations. The sublines were also tested in vitro with methotrexate and 5-fluorouracil. Again there were marked differences in sensitivity to inhibition of cell division by the drugs. The relative sensitivities in vitro did not correlate with observations in vivo. The existence of subpopulations of tumor cells, differing in sensitivity to therapeutic agents, within a single neoplasm, presents a challenge to development of assays capable of predicting drug response and to the selection of combination therapies.

Adenocarcinoma↗
PubMed1977

Effect of sequence of administration of methotrexate, leucovorin, and 5-fluorouracil on mammary tumor growth and survival in syngeneic C3H mice.

The administration of methotrexate (1mg/kg), leucovorin (1 mg/kg), and (after a 1-hr interval) 5-fluorouracil (50 mg/kg) selectively suppresses antibody production in C3H mice without inhibiting, but even stimulating, cell-mediated immunity. The effect of this regimen, given at weekly intervals, was tested on the growth of recently arising syngeneic C3H/HeJ mammary tumors. Inhibition of growth was found in three types of experiments: (a) when treatment was begun 2 days after tumor implantation, (b) when it was begun 3 weeks after implantation, and (c) when it was begun after surgical enucleation of the tumor. The extent of the effect varied from tumor to tumor, but in all cases tumor incidence or growth was significantly inhibited. Comparison was made between the above regimen and two other sequences of administration of the same drugs, which are only weakly immunosuppressive of antibody production and which do not stimulate cell-mediated immunity. Survival of tumor-bearing mice was greater with the administration of methotrexate, then leucovorin, followed by 5-fluorouracil, than it was with the other two administration schedules.

Animals↗
PubMed1976

Microcytotoxicity assay of immune responses to non-mammary tumor virus-induced, preneoplastic, and neoplastic mammary lesions in BALB/c mice.

Using a microcytotoxicity assay we have studied the immune responses to the preneoplastic, hyperplastic alveolar nodule (HAN) lines D1 and D2 and to the mammary tumors arising spontaneously from them in BALB/c mice. Lymph node cells (LNC) from mice bearing HAN implants, or from mice whose implants had been removed greater than 1 week prior to testing, failed significantly to inhibit survival of HAN cells in culture. Specific inhibition of HAN cells was found, however, in 9 of 28 experiments with LNC from mice whose implants had been removed within the week of testing, and not with LNC from sham-operated controls. On the other hand, increased survival of HAN cells was also seen with LNC from sensitized, as opposed to normal, mice. This was more frequent for tests with D1 than with D2 HAN cells (38 versus 9%) and when the LNC donors were still bearing HAN IMPLANTs (60% of tests versus 27% when implants removed). Following sensitization by implantation and subsequent removal of D1 or D2 tumors, LNC-mediated inhibition of tumor cell survival, specific for each tumor, was found in about 25% of the tests. Increased survival of tumor cells, however, was seen in 30 to 40% of the tests. This increased survival cross-reacted between D1 and D2 tumors and between D1-D2 and mammary tumor virus-induced tumors, but not between D1-D2 and chemically induced mammary tumors or fibrosarcomas. Increased survival could be blocked by sera from sensitized mice. In contrast to mammary tumor virus-induced mammary lesions, the immune responses to D1 and D2 HAN lines and tumors are "weak" and indeed perhaps stimulate hyperplastic and neoplastic cell survival.

Animals↗
PubMed1975

Evaluation of cell-mediated reactivity and serum blocking factors in melanoma patients on chemotherapy.

Sequential assays for cell-mediated reactivity (CMR) and serum blocking factor (SBF) were performed in a group of 12 melanoma patients who were treated with one or both of the clinically available imidazole carboxamide derivatives, DTIC and TIC Mustard, in order to consider the effects of treatment and changing patterns of disease on the results of in vitro tests in individual patients. Microcytotoxicity assays and the dilute agar colony inhibition test were employed. Of the 12 patients, 8 had no change in CMR and 5 had no change in SBF. Three patients demonstrated a fall in both CMR and SBF to nondetectable levels, and 3 additional patients showed a fall in SBF only. From these results, we conclude that there is no significant depression of CMR in melanoma patients by either of the imidazole carboxamide derivatives used. The results of SBF are less conclusive and more open to question, since it is just a likely that any depression to undetectable levels may be due to a change in disease status rather than to coincident drug use. It appears that microcytotoxicity assay results on individual patients may be fortuitous and difficult to interpret, even though results seen in patients as a group indicate important trends. The microcytotoxicity assay is a useful tool for the experimental tumor immunologist, but its clinical usefulness in individual patients is limited.

Adult↗
PubMed1975

Stimulation of hemolysin plaque-forming cells by idoxuridine.

5-Iodo-2'-deoxyuridine markedly stimulates the production of hemolysin plaque-forming cells (HPFC) to sheep red blood cells in C3HeB/FeJ and A/J male and female mice. The degree of stimulation is dose dependent over a range of 50 to 200 mg/kg. Stimulation is observed when drug is given on the day of antigen administration, or up to 3 days thereafter, but not when given before antigen administration or 4 days thereafter. The stimulatory effect of IUdR given on day 2 after antigen is still noted on Day 15, but the time of HPFC production is not prolonged beyond that in controls. Both 19S and 7S HPFC are increased, although the effect on the latter is less pronounced. In addition to stimulating production of HPFC in immunized animals, 5-iodo-2'-deoxyuridine increases background HPFC production in nonimmunized mice by 250% when assayed on the day after treatment.

Animals↗
PubMed1975

Correction of a murine mammary tumor virus-associated immunological depression by selective immunosuppression with cytosine arabinoside.

Mammary tumor virus (MTV) infection has been shown to be associated with a diminished hypersensitive reaction to methylated bovine serum albumin. Since methylated bovine serum albumin-induced hypersensitivity appears to be a mixed [humoral versus cell-mediated immunity (CMI)] reaction, the deficit in reactivity could be caused by, among other things, a direct depression of CMI or an increase in a humoral, blocking component. Assay of oxazolone-induced contact sensitivity and phytohemagglutinin-induced lymphocyte stimulation revealed normal or greater than normal CMI in MTV-positive animals. Treatment of MTV-positive and -negative animals with a regimen of cytosine arabinoside designed to inhibit only humoral immunity and leave CMI intact, corrected the deficit in methylated bovine serum albumin reactivity in MTV-positive mice. Thus, it is suggested that MTV infection may facilitate the production of interfering or blocking humoral immunity.

Animals↗